3-Methyl-phenanthrene (3-MP) disrupts the electrical and contractile activity of the heart of the polar fish, navaga cod (Eleginus nawaga)

Tatiana S Filatova; Vladislav S Kuzmin; Irina Dzhumaniiazova; Oksana B Pustovit; Denis V Abramochkin; Holly A Shiels

doi:10.1016/j.chemosphere.2024.142089

3-Methyl-phenanthrene (3-MP) disrupts the electrical and contractile activity of the heart of the polar fish, navaga cod (Eleginus nawaga)

Chemosphere. 2024 Jun:357:142089. doi: 10.1016/j.chemosphere.2024.142089. Epub 2024 Apr 19.

Authors

Tatiana S Filatova¹, Vladislav S Kuzmin¹, Irina Dzhumaniiazova¹, Oksana B Pustovit¹, Denis V Abramochkin², Holly A Shiels³

Affiliations

¹ Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia.
² Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia; Laboratory of Cardiac Electrophysiology, Chazov National Medical Research Center for Cardiology, Moscow, Russia; Department of Physiology, Pirogov Russian National Research Medical University, Ostrovityanova str., 1, Moscow, Russia.
³ Faculty of Biology, Medicine and Health, Core Technology Facility, 46 Grafton Street, University of Manchester, Manchester, M13 9NT, UK. Electronic address: holly.shiels@manchester.ac.uk.

PMID: 38643846
DOI: 10.1016/j.chemosphere.2024.142089

Abstract

Alkylated polycyclic aromatic hydrocarbons are abundant in crude oil and are enriched during petroleum refinement but knowledge of their cardiotoxicity remains limited. Polycyclic aromatic hydrocarbons (PAHs) are considered the main hazardous components in crude oil and the tricyclic PAH phenanthrene has been singled out for its direct effects on cardiac tissue in mammals and fish. Here we test the impact of the monomethylated phenanthrene, 3-methylphenanthrene (3-MP), on the contractile and electrical function of the atrium and ventricle of a polar fish, the navaga cod (Eleginus nawaga). Using patch-clamp electrophysiology in atrial and ventricular cardiomyocytes we show that 3-MP is a potent inhibitor of the delayed rectifier current I_Kr (IC50 = 0.25 μM) and prolongs ventricular action potential duration. Unlike the parent compound phenanthrene, 3-MP did not reduce the amplitude of the L-type Ca²⁺ current (I_Ca) but it accelerated current inactivation thus reducing charge transfer across the myocyte membrane and compromising pressure development of the whole heart. 3-MP was a potent inhibitor (IC50 = 4.7 μM) of the sodium current (I_Na), slowing the upstroke of the action potential in isolated cells, slowing conduction velocity across the atrium measured with optical mapping, and increasing atrio-ventricular delay in a working whole heart preparation. Together, these findings reveal the strong cardiotoxic potential of this phenanthrene derivative on the fish heart. As 3-MP and other alkylated phenanthrenes comprise a large fraction of the PAHs in crude oil mixtures, these findings are worrisome for Arctic species facing increasing incidence of spills and leaks from the petroleum industry. 3-MP is also a major component of polluted air but is not routinely measured. This is also of concern if the hearts of humans and other terrestrial animals respond to this PAH in a similar manner to fish.

Keywords: Alkylated polycyclic aromatic hydrocarbons; Arctic; Cardiac toxicity; Depolarization; Erg-channel; I(Ca); I(Kr); I(Na); Repolarization.

MeSH terms

Action Potentials / drug effects
Animals
Heart* / drug effects
Heart* / physiology
Myocytes, Cardiac* / drug effects
Myocytes, Cardiac* / metabolism
Perciformes / physiology
Phenanthrenes* / toxicity
Polycyclic Aromatic Hydrocarbons / toxicity
Water Pollutants, Chemical / toxicity

Substances

Phenanthrenes
Water Pollutants, Chemical
Polycyclic Aromatic Hydrocarbons
phenanthrene